Sialic acid compositions for the use of inhibiting and treating coronavirus infection

ABSTRACT

The present invention relates to the use of compositions comprising sialic acid to inhibit or treat coronavirus infections, and in particular those caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2).

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Prov. Appl. 63/003,477 filedApr. 1, 2020, the entire contents of which are incorporated herein byreference.

FIELD OF THE INVENTION

The present invention relates to the use of compositions comprisingsialic acid to inhibit or treat coronavirus infections, and inparticular those caused by SARS-CoV-2 (Severe Acute Respiratory SyndromeCoronavirus 2).

BACKGROUND OF THE INVENTION

Coronaviruses are a family of viruses that can cause illnesses such asthe common cold, severe acute respiratory syndrome (SARS) and MiddleEast respiratory syndrome (MERS). In 2019, a new coronavirus wasidentified as the cause of a disease outbreak that originated in China.The virus is now known as the severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2). The disease it causes is called coronavirusdisease 2019 (COVID-19). Cases of COVID-19 have been reported around theworld and WHO declared a global pandemic in March 2020.

Signs and symptoms of COVID-19 may appear two to 14 days after exposureand can include: fever; cough; and shortness of breath or difficultybreathing. Other symptoms can include: tiredness; aches; runny nose; andsore throat. The severity of COVID-19 symptoms can range from very mildto severe. Some people have no symptoms. People who are older or haveexisting chronic medical conditions, such as heart or lung disease ordiabetes, may be at higher risk of serious illness.

What is needed in the art are safe compositions for inhibiting ortreating infection by SARS-CoV-2.

SUMMARY OF THE INVENTION

The present invention relates to the use of compositions comprisingsialic acid to inhibit or treat coronavirus infections, and inparticular those caused by SARS-CoV-2 (Severe Acute Respiratory SyndromeCoronavirus 2).

Accordingly, in some preferred embodiments, the present inventionprovides methods for treating or inhibiting infection by SARS-CoV-2(Severe Acute Respiratory Syndrome Coronavirus 2), in a human or animalsubject, the method comprising: administering a composition comprisingsialic acid in an effective concentration to the subject underconditions such that infection by SARS-CoV-2 is inhibited or treated.

In some preferred embodiments, the present invention provides methodsfor prophylaxis of infection by SARS-CoV-2 (Severe Acute RespiratorySyndrome Coronavirus 2), in a human or animal subject, the methodcomprising: administering a composition comprising sialic acid in aneffective concentration to the subject under conditions such thatinfection by SARS-CoV-2 is inhibited.

In some preferred embodiments, the present invention provides sialicacid for use in treating or inhibiting infection by SARS-CoV-2 (SevereAcute Respiratory Syndrome Coronavirus 2) in a human or animal subject.

In some preferred embodiments, the present invention provides sialicacid for use in prophylaxis of SARS-CoV-2 (Severe Acute RespiratorySyndrome Coronavirus 2) infection in a human or animal subject.

In some preferred embodiments, the sialic acid is elected from the groupconsisting of n-acetylneuraminic acid (NANA) and n-glycolylneuraminicacid (NGNA). In some preferred embodiments, the sialic acid is NANA.

In some preferred embodiments, the sialic acid is administeredintranasally. In some preferred embodiments, the effective concentrationof sialic acid is from about 0.1 to about 100 mg/ml in an aqueoussolution. In some preferred embodiments, effective concentration ofsialic is from about 0.5 to about 50 mg/ml in an aqueous solution. Insome preferred embodiments, the daily dosage of sialic acid is fromabout 0.1 to 100 mg sialic acid/nostril/day. In some preferredembodiments, the daily dosage of sialic acid is from about 0.1 to 10 mgsialic acid/nostril/day. In some preferred embodiments, the pH ofcomposition comprising sialic acid, preferably in aqueous solution, isfrom 2.0 to 4.0. In some preferred embodiments, the pH of compositioncomprising sialic acid, preferably in aqueous solution, is from 2.5 to3.7. In some preferred embodiments, the pH of composition comprisingsialic acid, preferably in aqueous solution, is from 2.8 to 3.2. In somepreferred embodiments, the daily dosage of sialic acid is delivered infrom 2 to 8 administrations per day. In some preferred embodiments, thecomposition further comprises a thixotropic agent.

In some preferred embodiments, the sialic acid is administered orally.In some preferred embodiments, the daily dosage of sialic acid is from20 to 200 grams. In some preferred embodiments, the daily dosage ofsialic acid is from 50 to 150 grams. In some preferred embodiments, thedaily dosage is administered in from 1 to 20 doses. In some preferredembodiments, the sialic acid is administered as a aqueous solution. Insome preferred embodiments, the aqueous solution comprising anadditional agent selected from the group consisting of a flavoringagent, a stabilization agent and a preservative agent, wherein theadditional agent does not naturally occur with sialic acid.

In some preferred embodiments, the subject is at risk for infection bySARS-CoV-2.

In some preferred embodiments, the subject has COVID-19.

Additional embodiments are described herein.

Definitions

As used herein, the term “SARS-CoV-2 (severe acute respiratory syndromecoronavirus 2)” includes any strain of coronavirus identified as beingSARS-CoV-2 including mutants of SARS-CoV-2 reference genomic sequences.

As used herein, the term “inhibits” when used in reference to infectionby SARS-CoV-2 refers to a reduction in infection in subjects exposed toSARS-CoV-2.

A “patient,” “subject,” or “individual” are used interchangeably andrefer to either a human or a non-human animal. These terms includemammals, such as humans, primates, livestock animals (including bovines,porcines, etc.), companion animals (e.g., canines, felines, etc.) androdents (e.g., mice and rats).

“Administering” or “administration of” a substance, a compound or anagent to a subject can be carried out using one of a variety of methodsknown to those skilled in the art. For example, sialic acid can beadministered, intravenously, arterially, intradermally,intra-muscularly, intraperitonealy, intravenously, subcutaneously,sublingually, orally (by ingestion), intranasally (by inhalation),intraspinally, intracerebrally, and transdermally (by absorption, e.g.,through a skin duct). A compound or agent can also appropriately beintroduced by rechargeable or biodegradable polymeric devices or otherdevices, e.g., patches and pumps, or formulations, which provide for theextended, slow or controlled release of the compound or agent.Administering can also be performed, for example, once, a plurality oftimes, and/or over one or more extended periods. In some aspects, theadministration includes both direct administration, includingself-administration, and indirect administration, including the act ofprescribing a drug. For example, as used herein, a physician whoinstructs a patient to self-administer a drug, or to have the drugadministered by another and/or who provides a patient with aprescription for a drug is administering the drug to the patient.

A “therapeutically effective amount” or a “therapeutically effectivedose” of a drug or agent, such as sialic acid, is an amount of a drug oran agent that, when administered to a subject will have the intendedtherapeutic effect. The full therapeutic effect does not necessarilyoccur by administration of one dose, and may occur only afteradministration of a series of doses. Thus, a therapeutically effectiveamount may be administered in one or more administrations. The preciseeffective amount needed for a subject will depend upon, for example, thesubject's size, health and age, the nature and extent of symptoms of thecondition being treated, such as COVID-19. The skilled worker canreadily determine the effective amount for a given situation by routineexperimentation.

A “prophylactically effective amount” or a “prophylactically effectivedose” of a drug or agent, such as sialic acid, is an amount of a drug oran agent that, when administered to a subject will have the intendedprophylactic effect. The full prophylactic effect does not necessarilyoccur by administration of one dose, and may occur only afteradministration of a series of doses. Thus, a prophylactically effectiveamount may be administered in one or more administrations. The preciseeffective amount needed for a subject will depend upon, for example, thesubject's size, health and age, the nature and extent of symptoms of thecondition being treated, such as SARS-CoV-2 infection. The skilledworker can readily determine the effective amount for a given situationby routine experimentation. “Treating” a condition or patient refers totaking steps to obtain beneficial or desired results, including clinicalresults. Beneficial or desired clinical results include, but are notlimited to, alleviation, amelioration, or slowing the progression, ofone or more symptoms associated with COVID-19. In certain embodiments,treatment may be prophylactic, such as for the prevention of infectionby SARS-CoV-2.

As used herein, the term “dietary supplement” refers to a small amountof a compound for supplementation of a human or animal diet packaged insingle or multiple does units. Dietary supplements do not generallyprovide significant amounts of calories but may contain othermicronutrients (e.g., vitamins or minerals).

As used herein, the term “nutritional supplement” refers to acomposition comprising a “dietary supplement” in combination with asource of calories. In some embodiments, nutritional supplements aremeal replacements or supplements (e.g., nutrient or energy bars ornutrient beverages or concentrates).

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 provides data from one replicate showing infection of cells byCoV-OC43 at different concentrations of either Neu5Ac or Neu5Gc.

FIG. 2 provides data from another replicate showing infection of cellsby CoV-OC43 at different concentrations of either Neu5Ac or Neu5Gc.

FIG. 3 provides data from an experiment where inhibition of infection byNeu5Ac is compared to a control sugar, galactose.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to the use of compositions comprisingsialic acid to inhibit or treat coronavirus infections, and inparticular those caused by SARS-CoV-2 (Severe Acute Respiratory SyndromeCoronavirus 2).

Sialic acid is the generic name for N- or O-substituted derivatives ofneuraminic acid, a monosaccharide with nine carbon atoms. The substanceswere first described in saliva, hence its name after the Greek wordsaliva: sialon. Sialic acids are found naturally in the end of the denseand complex braid of sugar molecules, proteins and lipids on cellsurfaces and on many soluble proteins. Molecular, cellular and geneticstudies show that sialic acids participate in the control of cell andcell matrix interactions, intermolecular interactions on cell surfacesand in interactions with other molecules in the cell's immediateextracellular environment 1.

Sialic acids are a family of nine carbon keto-aldononulosonic acidspresented at the terminal ends of glycans on cellular membranes. Theyare abundantly displayed on the surfaces of vertebrate cells, andparticularly on all mucosal surfaces. N-acetyl neuraminic acid (Neu5Ac)is the most common form in mammalian cells.

Neu5Ac can be transformed into Neu5Gc with the enzyme CMAH (cytidinemonophosphate—N-acetylneuraminic acid hydroxylase). This enzyme is notfound in humans due to one deletion in the gene encoding it. One assumestherefore that man has in prehistoric times lost the functionality ofthis gene and thus the ability to transform NeuAc into Neu5Gc. Unlikeanimals and some others organisms, humans can only synthesize Neu5Ac.

The two most common sialic acids are N-acetyl neuraminic acid (Neu5Ac)and N-glycolylneuraminic acid (Neu5Gc). Carbon atom No. 5 in Neu5AC(square) can be enzymatically modified into one N-acetyl group andfurther hydroxylated to form Neu5Gc (circle). Hydroxyl group on severalcarbon atoms (C4, C7; C8 and C9) may further be modified, for examplewith O-acetyl, O-sulfate, O-lactyl, O-methyl and O-phosphate groups. Thesialic acids are attached to carbohydrate chains on glycoproteins andglycolipids via different glucoside bonds. The most common bonds areα2,3 binding to the galactose moiety, α2,6 binding to galactose or tothe N-acetylgalactosamine moiety, and α2.8 binding to another sialicacid moiety on a glycan. Sialic acids cleave the airway epithelium—andcan act as receptors for viruses. Newer research with glycan microarraysand other sophisticated methods shows the complexity of the interactionsbetween sialic acid-containing receptors on cell surfaces and virusesproteins. This provides opportunities for studies of how viruses adhereto cell surfaces in airway epithelium (4).

According to Schalcter (2017)(5) Neu5Ac is rapidly absorbed afteringestion. It is also quickly excreted via urine. The highestconcentration of sialic acids is found in saliva, urine and human brain.

The structure of Neu5Ac, features four protruding functional groups(carboxylate, hydroxyl, N-acetyl and glycerol functions). This largenumber of functional groups enables sialic acids to participate in anumber of hydrogen bonds, salt bridges and non-polar interactions at thesame time. Since sialic acid is typically located at the terminus of aglycan, its binding sites are easily accessible for interactions. Alarge number of viruses, including many serious human pathogens (forexample human Influenza A, B and C, Coxsackievirus A24 variant andenterovirus 70, human JC and BK polyomaviruses, Rotaviruses) use sialicacid in sialylated oligosaccharides for cell attachment. Neu et al.,Viruses and Sialic Acids: Rules of Engagement. Curr Opin Struct Biol.,(2011) 21(5), 610-618).

In most cases, interactions between a viral attachment protein and itsglycan receptor involve primarily the sialic acid itself, which is boundwith a relatively small contact area in a solvent-exposed region of thevirus protein. Consistent with this, the affinities of such interactionsare very low. Many of the viruses achieve remarkable specificity forsialylated oligosaccharide by establishing a secondary small number ofauxiliary interactions with functional groups that lie beyond the sialicacid. After binding, they use different mechanisms (endocytosis,pinocytosis, fusion) to enter the cell in order to take over the systemfor virus replication. A recent publication (Tortorici et al.,Structural basis for human coronavirus attachment to sialic acidreceptors. Nat Struct Mol Biol. 2019 June; 26(6):481-489) proposes thestructure of the human Coronavirus site binding to 9-0-acetylated sialicacid at mucosa membrane.

For viruses that are able to multiply and create an infection, virusesshould not just stick to epithelial surface, but also enzymaticallypenetrate the cell to use the cell's own replication machinery.Furthermore, new viral particles may come out of the cell. The “opening”of cell membranes can occur via a neuraminidase—an enzyme that cleavessialic acid from glycoconjugates. The virus enzyme thus provides foradditional spread of new viral particles. Studies have shown that theywill also be able to neutralize silicic acid-containing solubleproteins, which will otherwise interfere with surface bonding viruses(6, 7).

Despite many decades of research there are still relatively feweffective anti-viral compounds in comparison to the human disease burdeninflicted by viruses. Coupled with the high mutation rate of certainviruses, which enable anti-viral resistant mutants to arise withalarming speed and frequency, the need for a generic anti-viral agent isas important now as it ever has been.

Accordingly, provided herein are compositions comprising sialic acid foruse in treating or inhibiting infection by SARS-CoV-2. It iscontemplated that administration of sialic acid increases the naturalcontent of sialic acid in the nasal mucosa. In some preferredembodiments, the sialic acid is delivered directly to the nasal mucosavia a spray, gel, or other solution containing an effective amount ofsialic acid. In some preferred embodiments, the sialic acid is NANA. Thepresent invention is not limited to any particular mechanism of action.Nevertheless, it is contemplated that the administered sialic acidmolecules cover the epithelium of the respiratory tract and can act asreceptors for “hooking” the viruses. In other words, the free sialicacid molecules (not attached to the nasal mucosa) competitively bindsoluble virus particles, thus inhibiting the attachment of virus to thenasal epithelium. Since the free sialic acid is in excess, the bindingto cell bound receptors and transport into the cells is lowered, hencethe risk of virus infection is decreased and infection is inhibited.

The use of a variety of sialic acids is contemplated. In someembodiments, the sialic acids or sialic acid precursors have a purityselected from the group consisting of greater than 90%, 95%, 99%, and99.5% pure. In some preferred embodiments, the sialic acid or sialicacid precursor is selected from the group consisting ofn-acetylneuraminic acid (NANA), n-glycolylneuraminic acid (NGNA),N-Acetyl-D-mannosamine, and combinations thereof. In other preferredembodiments, the composition may comprise one or more of the followingsialic acids: Neuraminic acid, 5-N-Acetyl-4-O-acetyl-neuraminic acid,5-N-Acetyl-7-O-acetyl-neuraminic acid, 5-N-Acetyl-8-O-acetyl-neuraminicacid, 5-N-Acetyl-9-O-acetyl-neuraminic acid,5-N-Acetyl-4,9-di-O-acetyl-neuraminic acid,5-N-Acetyl-7,9-di-O-acetyl-neuraminic acid,5-N-Acetyl-8,9-di-O-acetyl-neuraminic acid,5-N-Acetyl-7,8,9-tri-O-acetyl-neuraminic acid,5-N-Acetyl-9-O-L-lactyl-acetyl-neuraminic acid, 5-N-Acetyl-4-O-acetylO-lactyl-acetyl-neuraminic acid, 5-N-Acetyl-8-O-methyl-neuraminic acid,5-N-Acetyl-9 acetyl-8-O-methyl-neuraminic acid,5-N-Acetyl-8-O-sulpho-neuraminic acid, 5-N-Acetyl O-phosphoro-neuraminicacid, 5-N-Acetyl-2-deoxy-2,3-didehydro-neuraminic acid,5-N-Acetyl-9-O-acetyl-2-deoxy-2,3-didehydro-neuraminic acid,5-N-Acetyl-2-deoxy-2,3-didehydro-9-O-lactyl-neuraminic acid,5-N-Acetyl-2,7-anhydro-neuraminic acid,4-O-Acetyl-5-N-glycolyl-neuraminic acid,7-O-Acetyl-5-N-glycolyl-neuraminic acid,8-O-Acetyl-5-N-glycolyl-neuraminic acid,9-O-Acetyl-5-N-glycolyl-neuraminic acid,7,9-Di-O-acetyl-5-N-glycolyl-neuraminic acid,8,9-Di-O-acetyl-5-N-glycolyl-neuraminic acid,7,8,9-Tri-O-acetyl-5-N-glycolyl-neuraminic acid,5-N-glycolyl-9-O-lactyl-neuraminic acid,5-N-glycolyl-8-O-methyl-neuraminic acid,9-O-Acetyl-5-N-glycolyl-8-O-methyl-neuraminic acid,7,9-di-O-Acetyl-5-N-glycolyl-8-O-methyl-neuraminic acid,5-N-glycolyl-8-O-sulpho-neuraminic acid, N-(O-acetyl)glycolylneuraminicacid, N-(O-Methyl)glycolylneuraminic acid,2-Deoxy-2,3-didehydro-5-N-glycolyl-neuraminic acid,9-O-Acetyl-2-deoxy-2,3-didehydo-5-N-glycolyl-neuraminic acid,2-Deoxy-2,3-didehydro-5-N-glycolyl-9-O-lactyl-neuraminic acid,2-Deoxy-2,3-didehydro-5-N-glycolyl-8-O-methyl-neuraminic acid,2,7-Anhydro-5-N-glycolyl-neuraminic acid,2,7-Anhydro-5-N-glycolyl-8-O-methyl-neuraminic acid,2-Keto-3-deoxynononic acid, and 9-O-Acetyl-2-keto-3-deoxynononic acid.

In some particularly preferred embodiments, the sialic acid is NANA.

Exemplary formulations are described in detail below. However, in someembodiments, the sialic acid is formulated as a lotion, spray, gel,ointment, powder, aqueous or non-aqueous solution for topical,intranasal, intravaginal, intraanal, or sublingual administration; as acapsule, powder, or tablet for enteral administration; or as a solutionfor parenteral administration.

Sialic compositions of the present invention may be delivered in anysuitable format. In some embodiments, the sialic acid is preferablyabout greater than 90%, 95%, 99% or 99.9% pure. In some embodiments, thesialic acid is HPLC purified. For example, NANA can be purchasedcommercially from, for example, Sigma Chemical Company, St. Louis, MO.

In some embodiments, the present invention provides methods of treating,alleviating, ameliorating, or inhibiting infection by a SARS-CoV-2, orreducing symptoms or outbreaks associated with infection by SARS-CoV-2,comprising administering an effective concentration of sialic acid(e.g., NANA). In some preferred embodiments, an effective concentrationof sialic acid (e.g., NANA) is from about 0.1 to about 10 mg/ml in anaqueous solution, for example, for treating, alleviating, ameliorating,reducing or inhibiting infection by SARS-CoV-2 or symptoms associatedwith SARS-CoV-2. In some preferred embodiments, the effectiveconcentration of sialic acid (e.g., NANA) is from about 0.5 to about 100mg/ml in an aqueous solution. In some preferred embodiments, theeffective concentration of sialic acid (e.g., NANA) is from about 0.5 toabout 50 mg/ml in an aqueous solution. In some preferred embodiments,the effective concentration of sialic acid (e.g., NANA) is from about0.5 to about 5 mg/ml in an aqueous solution. In some preferredembodiments, the daily dosage of sialic acid (e.g., NANA) is from about0.1 to 5.0 mg sialic acid (e.g., NANA)/nostril/day. In some preferredembodiments, the daily dosage of sialic acid (e.g., NANA) is from about0.1 to 1.0 mg sialic acid (e.g., NANA)/nostril/day. In some preferredembodiments, the effective concentration of sialic acid (e.g., NANA) isfrom about 0.5 to about 100 mg/ml in an aqueous solution. In somepreferred embodiments, the daily dosage of sialic acid (e.g., NANA) isfrom about 0.1 to 100 mg sialic acid (e.g., NANA)/nostril/day. In somepreferred embodiments, the daily dosage of sialic acid (e.g., NANA) isfrom about 0.1 to 50 mg sialic acid (e.g., NANA)/nostril/day.

In some preferred embodiments, the pH of composition comprising thesialic acid (e.g., NANA), preferably in aqueous solution, is from 2.0 to4.0. In some preferred embodiments, the pH of composition comprising thesialic acid (e.g., NANA), preferably in aqueous solution, is from 2.5 to3.7. In some preferred embodiments, the pH of composition comprising thesialic acid (e.g., NANA), preferably in aqueous solution, is from 2.8 to3.2.

In some embodiments, the sialic acid (e.g., NANA) compositions areprovided in an aqueous solution, including gels, suitable for use as aspray or mist. In some embodiments, the aqueous sialic acid (e.g., NANA)solution is incorporated into a pump-spray container, such asprecompression pump, or a device such as a nebulizer or cold mistsystem, for delivery into the nose, mouth or lungs as a fine mist orspray. In some preferred embodiments, the present invention provides aspray bottle configured for application of a nasal spray to the nose ofanimal or human containing any of the compositions described above.

In some preferred embodiments, the daily dosage of sialic acid (e.g.,NANA) is from about 0.1 to 5.0 mg sialic acid (e.g., NANA) nostril/day.In some preferred embodiments, the daily dosage of NANA is from about0.1 to 1.0 mg sialic acid (e.g., NANA)/nostril/day. In some preferredembodiments, the spray bottle is calibrated to deliver a spray dosecomprising from 0.03 to 1.0 mg sialic acid (e.g., NANA)/spray. In somepreferred embodiments, the spray bottle is calibrated to deliver a spraydose comprising from 0.05 to 0.3 mg sialic acid (e.g., NANA)/spray. Insome preferred embodiments, the daily dosage of sialic acid (e.g., NANA)is delivered in from 2 to 8 administrations per day from the spraybottle, i.e., from 2 to 8 pumps of the spray to each nostril.

In some preferred embodiments, the daily dosage of sialic acid (e.g.,NANA) is from about 0.1 to 100 mg sialic acid (e.g., NANA) nostril/day.In some preferred embodiments, the daily dosage of NANA is from about1.0 to 100 mg sialic acid (e.g., NANA)/nostril/day. In some preferredembodiments, the spray bottle is calibrated to deliver a spray dosecomprising from 1.0 to 100 mg sialic acid (e.g., NANA)/spray. In somepreferred embodiments, the spray bottle is calibrated to deliver a spraydose comprising from 1.0 to 50 mg sialic acid (e.g., NANA)/spray. Insome preferred embodiments, the daily dosage of sialic acid (e.g., NANA)is delivered in from 2 to 8 administrations per day from the spraybottle, i.e., from 2 to 8 pumps of the spray to each nostril.

In some embodiments, the composition further comprises a thixotropicagent (e.g., including but not limited to, fucoidans, alginates orchitosan). In some embodiments, the thixotropic agent is mannuronicacid. In some embodiments, the mannuronic acid is present in thecomposition at a w/w percent range of 0.01 to 2.0% (e.g., 0.01 to 1.0%or 0.1% to 0.5%).

In some embodiments, the sialic acid (e.g., NANA) compositions of thepresent invention contain a pharmaceutically acceptable excipient whichis effective in forming a thixotropic suspension of the solid particlesof medicament comprising the composition, such as those described inU.S. Pat. No. 7,122,206. The excipient is preferably present in anamount which maintains the particles of medicament suspended in thecomposition during non-use and during spray of the composition into thenasal cavity, and also when the composition is deposited on the mucosalsurfaces of the nasal cavities or endothelial surfaces in the nasalcavity or elsewhere in the body. In some embodiments, the viscosity ofthe composition at rest is relatively high, for example, about 400 toabout 1000 cp. As the composition is subjected to shear forces, forexample, upon being subjected to forces involved in its being agitatedbefore spraying, the viscosity of the composition decreases (forexample, to about 50 to about 200 cp) and it flows readily through thespray device and exits therefrom in the form of a fine plume whichinfiltrates and deposits on the mucosal surfaces of at least thefollowing parts of the nose: the anterior regions of the nose (frontalnasal cavities); the frontal sinus; the maxillary sinuses; and theturbinates which overlie the conchas of the nasal cavities. Thus, theNANA compositions comprise a freely flowable liquid, and in sprayedform, a fine mist that finds its way to and deposits on the desiredmucosa. In deposited and relatively unstressed form, the compositionincreases in viscosity and assumes its gel-like form which includesparticles of the medicament suspended therein and which resists beingcleared from the nasal passages by the inherent mucocillary forces thatare present in the nasal cavities.

Any pharmaceutically acceptable material which is capable of maintainingthe solid particles of medicament dispersed substantially uniformly inthe composition and of imparting to the composition desired thixotropicproperties can be used. Such material is referred to as a “suspendingagent”. Examples of suspending agents include carboxmethylcellulose,veegum, tragacanth, bentonite, methylcellulose, and polyethyleneglycols. A preferred suspending agent is a mixture of microcrystallinecellulose and carboxymethylcellulose, the former being presentpreferably in a major amount, most preferably in an amount of about 85to about 95 wt. %, with the latter constituent comprising about 5 toabout 15 wt. % of the mixture.

The amount of suspending agent comprising the composition will varydepending on the particular medicament and amount used, the particularsuspending agent used, the nature and amounts of the other ingredientscomprising the composition, and the particular viscosity values that aredesired. Generally speaking, it is believed that the most widely usedcompositions will comprise about 1 to about 5 wt. % of the suspendingagent.

The sialic acid (e.g., NANA) compositions of the present inventionincludes preferably other ingredients which impart desired properties tothe composition. In some embodiments, dispersing or wetting agents areutilized. Any dispersing agent which is effective in wetting theparticles and which is pharmaceutically acceptable can be used. Examplesof dispersing agents that can be used are fatty alcohols, esters, andethers, including, for example, those sold under the trademarksPluronic, Tergitol, Span, and Tween. It is preferred to use ahydrophilic, non-ionic surfactant. Excellent results have been achievedutilizing sorbitan monooleatepolyoxyethylene which is available underthe trademark Polysorbate 80.

In some embodiments, the compositions comprise an anti-oxidant. Examplesof pharmaceutically acceptable anti-oxidants that can be used in thecomposition include ascorbic acid, sodium ascorbate, sodium bisulfite,sodium thiosulfate, 8-hydroxy quinoline, and N-acetyl cysterine. It isrecommended that the composition comprise about 0.001 to about 0.01 wt.% of the anti-oxidant.

Also, for stability purposes, the sialic acid (e.g., NANA) compositionsshould be protected from microbial contamination and growth. Examples ofpharmaceutically acceptable anti-microbial agents that can be used inthe composition include quaternary ammonium compounds, for example,benzalkonium chloride, benzethonium chloride, cetrimide, andcetylpyridinium chloride; mercurial agents, for example, phenylmercuricnitrate, phenylmercuric acetate, and thimerosal; alcoholic agents, forexample, chlorobutanol, phenylethyl alcohol, and benzyl alcohol;antibacterial esters, for example, esters of para-hydroxybenzoic acid;and other anti-microbial agents such as chlorhexidine, chlorocresol, andpolymyxin. It is recommended that the composition comprise about 0.001to about 1 wt. % of the anti-microbial agent.

As mentioned above, an aspect of the present invention comprises acomposition which is odorless and which contains a mixture ofstabilizing agents which function as an anti-oxidant and as ananti-microbial agent. The mixture comprises a quaternary ammoniumcompound that has anti-microbial properties and a material which isgenerally recognized as a chelating agent. The use in the composition ofthis combination of materials with the medicament, for example,triamcinolone acetonide, results in a highly stable composition that isresistant to oxidative degradation and to the growth of bacteria and thelike. In preferred form, the mixture comprises benzalkonium chloride anddisodium ethylenediamine tetraacetate.

The odorless composition generally will comprise about 0.004 to about0.02 wt. % of the quaternary ammonium compound and about 0.01 to about0.5 wt. % of the chelating agent. By virtue of the use of theaforementioned mixture of compounds, it is not necessary to include inthe composition a material which is considered an anti-oxidant.

The composition of the present invention includes preferably aniso-osmotic agent which functions to prevent irritation of nasal mucosaby the composition. Dextrose in anhydrous form is a preferrediso-osmotic agent. Examples of other pharmaceutically acceptableiso-osmotic agents which can be used include sodium chloride, dextroseand calcium chloride. It is recommended that the composition comprise upto about 5 wt. % of the iso-osmotic agent.

The sialic acid (e.g., NANA) compositions of the present invention canbe prepared in any suitable way. In preferred form, an aqueoussuspension of the solid particles of medicament and dispersing agent isformed and combined with an aqueous suspension which contains thesuspending agent. The former is preferably prepared by adding themedicament to an aqueous solution of the dispersing agent and mixingthoroughly. The latter is prepared by acidifying the water (pH about 4.7to about 5.3) prior to adding the suspending agent. In particularlypreferred form, an aqueous solution of the quaternary compound(anti-microbial agent) is added to the aqueous suspension of medicament,and the other ingredients (for example, iso-osmotic agent, anti-oxidantor chelating agent) are added to the thixotropic suspension. Each of theaforementioned batches of composition is mixed thoroughly before beingcombined. The preferred means of combining the batches of composition isto introduce one of the batches, preferably the “medicament” batch intothe bottom of the other batch, for example, by pumping the batchupwardly through the other batch. The composition comprising thecombined batches is mixed thoroughly. Use of the preferred method ofpreparation provides an efficient and effective way for formulating acomposition that has the solid particles of medicament substantiallyuniformly dispersed therein while avoiding problems that are generallyassociated with the preparation of water-based pharmaceuticalcompositions, for example, excessive foaming and non-uniformity of theparticle dispersement.

The amount of sialic acid (e.g., NANA) applied to each of the nasalpassages will vary depending on the nature of the condition beingtreated and the nature of the individual being treated. In somepreferred embodiments, the effective concentration of sialic acid (e.g.,NANA) is from about 0.1 to about 100 mg/ml in an aqueous solution. Insome preferred embodiments, the effective concentration of sialic acid(e.g., NANA) is from about 1.0 to about 100 mg/ml in an aqueoussolution. In some preferred embodiments, the effective concentration ofsialic acid (e.g., NANA) is from about 1.0 to about 50 mg/ml in anaqueous solution. In some preferred embodiments, the effectiveconcentration of sialic acid (e.g., NANA) is from about 0.1 to about 10mg/ml in an aqueous solution. In some preferred embodiments, theeffective concentration of sialic acid (e.g., NANA) is from about 0.5 toabout 5 mg/ml in an aqueous solution. In some preferred embodiments, thedaily dosage of sialic acid (e.g., NANA) is from about 0.001 to 0.1 mgsialic acid (e.g., NANA)/nostril/day. In some preferred embodiments, thedaily dosage of sialic acid (e.g., NANA) is from about 0.01 to 0.05 mgsialic acid (e.g., NANA)/nostril/day. In some preferred embodiments, thedaily dosage of sialic acid (e.g., NANA) is delivered in from 2 to 8administrations per day.

Accordingly, the present invention provides an article of manufacturecomprising a spray bottle having an sialic acid (e.g., NANA) solution orpowder therein for delivery into a body cavity such as the nose. Thespray bottle may preferably comprise a pump system for expelling theNANA composition from the bottle, such as a compression mump, spray pumpor precompression pump. In some preferred embodiments, the spray bottleis calibrated to deliver a spray dose comprising from 0.1 to 10 mgsialic acid (e.g., NANA)/spray. In some preferred embodiments, the spraybottle is calibrated to deliver a spray dose comprising from 0.001 to0.02 mg sialic acid (e.g., NANA)/spray. In some preferred embodiments,the spray bottle is calibrated to deliver a spray dose comprising from0.004 to 0.01 mg sialic acid (e.g., NANA)/spray.

In some embodiments, the present invention provides an article ofmanufacture that is a device that can be worn over a body cavity such asthe mouth or nose of an individual. In some embodiments, the device ismask, such as a surgical mask. In preferred embodiments, the maskcomprises a solid support or matrix, such as a polymer matrix or a wovenfabric matrix, into which an sialic acid (e.g., NANA) composition isincorporated. In some embodiments, the sialic acid (e.g., NANA)composition is spray coated onto the matrix as an aqueous solution, gelor powder. In some embodiments, when a breath is taken through the mask,viruses are inactivated as they contact the mask. In some embodiments,the matrix is coated with an sialic acid (e.g., NANA) composition toprovide from about 0.01 microgram to about 100 milligram sialic acid(e.g., NANA) per cm² of the matrix, preferably from about 1 microgram toabout 1 milligram sialic acid (e.g., NANA) per cm².

In some embodiments, sialic acid (e.g., NANA) is formulated for oraldelivery. The ingredients of the supplements of this invention arepreferably contained in acceptable excipients and/or carriers for oralconsumption. The actual form of the carrier, and thus, the supplementitself, is not critical. The carrier may be a liquid, gel, gelcap,capsule, powder, solid tablet (coated or non-coated), tea, or the like.The supplement is preferably in the form of a tablet or capsule and mostpreferably in the form of a hard gelatin capsule. Suitable excipientand/or carriers include maltodextrin, calcium carbonate, dicalciumphosphate, tricalcium phosphate, microcrystalline cellulose, dextrose,rice flour, magnesium stearate, stearic acid, croscarmellose sodium,sodium starch glycolate, crospovidone, sucrose, vegetable gums, lactose,methylcellulose, povidone, carboxymethylcellulose, corn starch, and thelike (including mixtures thereof). Preferred carriers include calciumcarbonate, magnesium stearate, maltodextrin, and mixtures thereof. Thevarious ingredients and the excipient and/or carrier are mixed andformed into the desired form using conventional techniques. The tabletor capsule of the present invention may be coated with an entericcoating that dissolves at a pH of about 6.0 to 7.0. A suitable entericcoating that dissolves in the small intestine but not in the stomach iscellulose acetate phthalate. Further details on techniques forformulation for and administration may be found in the latest edition ofRemington's Pharmaceutical Sciences (Maack Publishing Co., Easton, Pa.).

In some embodiments, the oral delivery vehicles described above areformulated so as to provide a daily dose of between 0.1 g and 10.0 g ofsialic acid (e.g., NANA), preferably between 0.5 and 2.0 g of NANA, andeven more preferably approximately 1.0 g of sialic acid (e.g., NANA). Insome embodiments, an effective amount of NANA is the amount needed toinhibit the growth and proliferation of a virus of interest or toinactivate the virus. In some embodiments, the effective amount is theamount of sialic acid (e.g., NANA) sufficient to provide a concentrationof NANA of from about 1 nanomolar to 10 micromolar at a site ofinterest, such as the circulating bloodstream or in a body cavity suchas the nasal passages or sinuses.

In some preferred embodiments, the sialic acid is administered orally.In some preferred embodiments, the daily dosage of sialic acid is from20 to 200 grams. In some preferred embodiments, the daily dosage ofsialic acid is from 50 to 150 grams. In some preferred embodiments, thedaily dosage is administered in from 1 to 20 doses. In some preferredembodiments, the sialic acid is administered as a aqueous solution. Insome preferred embodiments, the aqueous solution comprising anadditional agent selected from the group consisting of a flavoringagent, a stabilization agent and a preservative agent, wherein theadditional agent does not naturally occur with sialic acid.

In some embodiments, sialic acid (e.g., NANA) is provided in a fluidthat can be used for atmospheric treatment, such as by a mist. In someembodiments, the present invention provides a device comprising areservoir, a pump, and a nozzle, wherein the reservoir comprises a fluidcomprising sialic acid (e.g., NANA) that can be expelled via the pumpthrough the nozzle to provide a mist comprising sialic acid (e.g.,NANA). In some embodiments, the device is a humidifier, while in otherembodiments, the device is an automated mist dispenser. In someembodiments, the sialic acid (e.g., NANA) is provided as an aerosolspray in an appropriate aerosol spray dispensing device. Accordingly, insome embodiments, the present invention provides a device or compositioncomprising a sialic acid (e.g., NANA) and an aerosol propellant.Propellants include, but are not limited to, mixtures of volatilehydrocarbons, typically propane, n-butane and isobutene, dimethyl ether(DME), methyl ethyl ether, nitrous oxide, carbon dioxide andhydrofluoroalkanes (HFA): either HFA 134a (1,1,1,2,-tetrafluoroethane)or HFA 227 (1,1,1,2,3,3,3-heptafluoropropane) or combinations of thetwo. Typically, the sialic acid (e.g., NANA) fluid will be miscible withthe propellant. The sialic acid (e.g., NANA) fluid may preferably beformulated to be an aerosol mist, foaming gel, cream or lotion.

Modern aerosol spray products have three major parts; the can, the valveand the actuator or button. The can is most commonly lacquered tinplate(steel with a layer of tin) and may be made of 2 or 3 pieces of metalcrimped together. Aluminum cans are also common and are generally usedfor more expensive products. The valve is crimped to the rig of the can,the design of this component is important in determining the spray rate.The actuator is depressed by the user to open the valve; the shape andsize of the nozzle in the actuator controls the spread of the aerosolspray.

In some embodiments, the devices of the present invention comprise apiston barrier system. Packaging that uses a piston barrier system isoften used for highly viscous products such as post-foaming gels, thickcreams and lotions. The main benefit of the piston barrier system isthat is assures separation of the product from the propellant,maintaining the purity and integrity of the formulation throughout itsconsumer lifespan. The piston barrier system also provides a controlledand uniform product discharge rate with minimal product retention and iseconomical.

In some embodiments, the devices of the present invention comprise abag-in-can system (or BOV “bag on valve”). This system separates theproduct from the pressurizing agent with a hermetically-sealed,multi-layered laminated pouch, which maintains complete formulationintegrity so only pure product is dispensed. In this embodiment, theNANA fluid is provided in the bag. Among its many benefits, thebag-in-can system extends a product's shelf life. Other advantagesinclude all-attitude (360-degree) dispensing, quiet and non-chillingdischarge.

These devices find use in setting where an antiviral spray, foam, gel orother fluid is needed. For example, the devices find use in dispensingan antiviral mist to treat a desired environment or space, such as aroom in a building such as an office, kitchen, cubicle or lavatory, or avehicle such a train car, airplane, bus, or taxi, van or car, or animalconfinement facilities such as barns, abattoirs, poultry houses, etc.The devices can also be used to dispense sialic acid (e.g., NANA)containing fluids on a surface such as a countertop, floor, shower, etc.In some embodiments, the devices are used to inject the sialic acid(e.g., NANA)—containing mist into the ventilation system of a building,barn, or vehicle.

In still further embodiments, the present invention provides sialic acid(e.g., NANA) compositions that comprise sialic acid (e.g., NANA) in asolution, such as a normal saline solution, that can be applied to theeye. Accordingly, in some embodiments, the present invention provides anarticle of manufacture comprising a container equipped with a nozzle toprovide drops of an sialic acid (e.g., NANA) solution to the eye. It iscontemplated that in addition to effects in the eye and surroundingtissue, sialic acid (e.g., NANA) administration via the eye and tearchannel will directly access the sinuses and associated cavities. Thus,administration of sialic acid (e.g., NANA) and/or additionalantimicrobials or antivirals in eyedrops is an effective method ofadministration of sialic acid (e.g., NANA) or other compounds for thetreatment of eye infections, sinus infections, and systemic treatmentvia the eye and tear channel, and sinuses, mucus internal surfaces foreffective adsorption providing local and systemic treatments.

In other embodiments, the sialic acid (e.g., NANA) is provided as apowder or liquid suitable for adding by the consumer to a food orbeverage. For example, in some embodiments, the dietary supplement canbe administered to an individual in the form of a powder, for instanceto be used by mixing into a beverage, or by stirring into a semi-solidfood such as a pudding, topping, sauce, puree, cooked cereal, or saladdressing, for instance, or by otherwise adding to a food.

In some embodiments, the sialic acid (e.g., NANA) is provided in waterthat is supplied to farm animals, such as poultry, cattle, swine, sheepand the like, or used in water used in fisheries. In other embodiments,sialic acid (e.g., NANA) is provided in tap water or water bottles waterfor human use.

The sialic acid (e.g., NANA) compositions may comprise one or more inertingredients, especially if it is desirable to limit the number ofcalories added to the diet by the dietary supplement. For example, thedietary supplement of the present invention may also contain optionalingredients including, for example, herbs, vitamins, minerals,enhancers, colorants, sweeteners, flavorants, inert ingredients, and thelike. For example, the compositions of the present invention may containone or more of the following: asorbates (ascorbic acid, mineralascorbate salts, rose hips, acerola, and the like),dehydroepiandosterone (DHEA), Fo-Ti or Ho Shu Wu (herb common totraditional Asian treatments), Cat's Claw (ancient herbal ingredient),green tea (polyphenols), inositol, kelp, dulse, bioflavinoids,maltodextrin, nettles, niacin, niacinamide, rosemary, selenium, silica(silicon dioxide, silica gel, horsetail, shavegrass, and the like),spirulina, zinc, and the like. Such optional ingredients may be eithernaturally occurring or concentrated forms.

In some embodiments, the compositions further comprise vitamins andminerals including, but not limited to, calcium phosphate or acetate,tribasic; potassium phosphate, dibasic; magnesium sulfate or oxide; salt(sodium chloride); potassium chloride or acetate; ascorbic acid; ferricorthophosphate; niacinamide; zinc sulfate or oxide; calciumpantothenate; copper gluconate; riboflavin; beta-carotene; pyridoxinehydrochloride; thiamin mononitrate; folic acid; biotin; chromiumchloride or picolonate; potassium iodide; sodium selenate; sodiummolybdate; phylloquinone; vitamin D₃; cyanocobalamin; sodium selenite;copper sulfate; vitamin A; vitamin C; inositol; potassium iodide.Suitable dosages for vitamins and minerals may be obtained, for example,by consulting the U.S. RDA guidelines.

The present invention provides dietary supplements comprisingnutraceutical agents, preferably sialic acid (e.g., NANA) either byitself or in combination with one or more additional nutraceuticalsagents. Nutraceutical agents are natural, bioactive chemical compoundsthat have health promoting, disease preventing or medicinal properties.Examples of nutraceuticals include, but are not limited to, Allium cepa,Allium sativum, Aloe vera, Angelica Species, Naturally OccurringAntioxidants, Aspergillus oryzae Enzyme Therapy, barley grass,Bromelain, Carnitine, Carotenoids and Flavonoids, Catechin, CentellaAsiatica (Gotu kola), Coenzyme Q10, Chinese Prepared Medicines, Coleusforskohlii, Commiphora mukul, Conjugated Linoleic Acids (CLAs),Crataegus oxyacantha (Hawthorne), Curcuma longa (Turmeric), EchinaceaSpecies (Purple Coneflower), Eleutherococcus senticosus (SiberianGinseng), Ephedra Species, Dietary Fish Oil Consumption and Fish OilSupplementation, Genistein, Ginkgo biloba, Glycyrrhiza (Licorice),Hypericum Perforatum (St. John's Wort), Hydrastis (Goldenseal) and OtherBerberine-Containing Plants, Lactobacillus, Lobelia (Indian Tobacco),Melaleuca Alternifolia, Menaquinone, Mentha piperita, Panax ginseng,Pancreatic Enzymes, Piper Mythisticum, Procyanidolic Oligomers, Pygeumafricanum, Quercetin, Sarsaparilla Species, Serenoa repens (Sawpalmetto, Sabal serrulata), Silybum marianum (Milk Thistle),Rosemary/Lemon balm, Selenite, Tabebuia avellanedae (LaPacho), Taraxacumofficinale, Tanacetum parthenium (Feverfew), Taxol, Uva ursi(Bearberry), Vaccinium myrtillus (Blueberry), Valerian officinalis,Viscum album (Mistletoe), Vitamin A, Beta-Carotene and OtherCarotenoids, and Zingiber officinale(Ginger).

Several nutraceutical agents are used in treating viral disorders (e.g.,Genistein (in soy/red clover), rosemary/lemon balm, selenite, barleygrass, lauric acid, Phyllanthus amarus/niruri (see, e.g., Nicolson, G.(1998) J. Medicine 1:123-128; herein incorporated by reference in itsentirety). Additional anti viral nutraceutical agents include, but arenot limited to, catechins, flavonoids, Echinacea, and cascara.

EXAMPLES Example 1

A nasal spray is formulated that comprises 1 mg/ml n-acetylneuraminicacid (NANA) in a sterile 0.9% saline solution with a pH of 3.0. Theformulation may be provided in a 20 ml pump spray bottle calibrated todeliver an average of 140 sprays with 1 spray being delivered for eachpump of the bottle.

Example 2

A nasal spray is formulated that comprises 1 mg/ml n-glycolylneuraminicacid (NGNA) in a sterile 0.9% saline solution with a pH of 3.0. Theformulation may be provided in a 20 ml pump spray bottle calibrated todeliver an average of 140 sprays with 1 spray being delivered for eachpump of the bottle.

Example 3

The effectiveness of sialic acid (Neu5Ac or Neu5Gc) in preventing coronavirus infection was evaluated in vitro in a model system. Differentdilutions of the sialic acids were tested for their ability to inhibitinfection of cells with the test virus CoV-OC43. The results arepresented in FIGS. 1 to 3 . FIGS. 1 and 2 provide data from tworeplicates showing infection of cells by CoV-OC43 at differentconcentrations of either Neu5Ac or Neu5Gc (Neu5Ac left hand bars, Neu5Gcright hand bars). As can be seen, infection is inhibited in adose-dependent manner. FIG. 3 provides data from an experiment whereinhibition of infection by Neu5Ac (left hand bars) is compared to acontrol sugar, galactose (right hand bars). As can be seen, Neu5Acprevents infection as compared to the control.

REFERENCES

-   1 Ronald L. Schnaars, Rita Gerardy-Schahn, and Herbert Hildebrandt:    sialic Acids in the Brain: Gangliosides and Polysialic Acid Nervous    System Development, Stability, Disease, and Regeneration. Physiol    Rev. 2014 April; 94 (2): 461-518.doi: 10.1152/physrev.00033.2013-   2 Norbert Sprenger and Peter I. Duncan: sialic Acid Utilization.    2012 American Society for Nutrition. Adv. Nutr. 3: 392S-397S, 2012;    doi: 10.3945/m.111.001479.-   3 Jennifer E. Stencel-Baerenwald, Kerstin Reiss, Dirk M. Reiter,    Thilo Stehle, and Terence S. Dermody: The sweet spot: Defining    virus-sialic acid interactions. Nat Rev Microbiol. 2014 November; 12    (11): 739-749. doi: 10.1038/nrmicro3346.-   3 B Wang and J Brand-Miller: The role and potential of sialic acid    in human nutrition. Review.-   4 Ursula Neu, Johannes Bauer, and Thilo Stehle. Viruses and sialic    Acids: Rules of Engagement. Curr Opin Struct Biol. 2011 October; 21    (5): 610-618. doi: 10.1016/j.sbi.2011.08.009.-   5 Schalcter M: N-Acetylneuraminic Acid (Neu5Ac).    www.glyconutritionforlife.org/Science of    Glyconutrients/N-Acetylneuraminic Acid_(Neu5Ac) php-   6 Ajit Varki, sialic acids in human health and disease. Trends Mol    Med. 2008 August; 14 (8): 351-360. doi:    10.1016/j.molmed.2008.06.002.-   7 Thilo Stehle, Zaigham M. Khan: Rules and Exceptions: sialic Acid    Variants and Their Role in Determining Viral Tropism. Journal of    Virology p. 7696-7699 July 2014 Volume 88 Number 14-   8 Muriel Bardor, Dzung H. Nguyen, Sandra Diaz, and Ajit Varki:    Mechanism of Uptake and Incorporation of the Non-human sialic acid    N-Glycolylneuraminic Acid into Human Cells. J Biol Chem Vol. 280,    No. 6, Issue of February 11, pp. 4228-4237, 2005-   9 Newburg, D S: Do the binding properties of oligosaccharides in    milk protect human infants from gastrointestinal bacteria? J. Nutr.    127: 980S-984S, 1997.-   10 Heine, W; Wutzke, K D; Radke M. Sialic acid in breast milk and    infant formula food. Monatsschr Kinderheilkd. 1993 December; 141    (12): 946 to −50.-   11 Boehm, G and Stahl, B. Oligosaccharides in milk. J. Nutr 2007,    vol 137, p 847S-849S-   12 Martin-Sosa, S, Martin, M-J and Hueso, P: The Sialylated Fraction    of Milk oligosaccharides Ice Partially Responsible for Binding two    enterotoxigenic and Uropathogenic Escherichia coli Human Strains. J.    Nutr. 132: 3067-3072, 2002-   13 Samraj A N, Pearce O M, Laubli H, Crittenden A N, Bergfeld A K,    Banda K, Gregg C J, Bingman A E, Secrest P, Diaz S L, Varki N M,    Varki A.: A red meat-derived glycan promoter inflammation and cancer    progression. Proc Natl Acad Sci US A. 2015 Jan. 13; 112 (2): 542 to    −7. doi:10.1073/pnas.1417508112. Epub 2014 Dec. 29.-   14 GRAS Notice (GRN) No. 602    http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/default.htm    ORIGINAL SUBMISSION-   15 Choi, S H, Baldin, N., Wagner, V O (2I), Roy, S., Rose, J.,    Thosrud, B A, Pnothirath, P. & {umlaut over (R)}origh, CH 2014.    Safety evaluation of the human-identical milk monosaccharide sialic    acid (N-acetyl-D-neuraminic acid) in Sprague-Dawley rats. Regul.    Toxicol. Pharmacol., 70, 482 to −491.

All publications and patents mentioned in the above specification areherein incorporated by reference. Various modifications and variationsof the described method and system of the invention will be apparent tothose skilled in the art without departing from the scope and spirit ofthe invention. Although the invention has been described in connectionwith specific preferred embodiments, it should be understood that theinvention as claimed should not be unduly limited to such specificembodiments. Indeed, various modifications of the described modes forcarrying out the invention which are obvious to those skilled in therelevant fields are intended to be within the scope of the followingclaims.

1. A method for treating or inhibiting infection by SARS-CoV-2 (SevereAcute Respiratory Syndrome Coronavirus 2), in a human or animal subject,the method comprising: administering a composition comprising sialicacid in an effective concentration to the subject under conditions suchthat infection by SARS-CoV-2 is inhibited or treated.
 2. A method forprophylaxis of infection by SARS-CoV-2 (Severe Acute RespiratorySyndrome Coronavirus 2), in a human or animal subject, the methodcomprising: administering a composition comprising sialic acid in aneffective concentration to the subject under conditions such thatinfection by SARS-CoV-2 is inhibited. 3-4. (canceled)
 5. Method of claim1, wherein the sialic acid is elected from the group consisting ofn-acetylneuraminic acid (NANA) and n-glycolylneuraminic acid (NGNA). 6.Method of claim 5, wherein the sialic acid is NANA.
 7. Method of claim1, wherein the sialic acid is administered intranasally.
 8. Method ofclaim 7, wherein the effective concentration of sialic acid is fromabout 0.1 to about 100 mg/ml in an aqueous solution.
 9. Method of claim7, wherein the effective concentration of sialic is from about 0.5 toabout 50 mg/ml in an aqueous solution.
 10. Method of claim 8, whereinthe daily dosage of sialic acid is from about 0.1 to 100 mg sialicacid/nostril/day.
 11. Method of claim 8, wherein the daily dosage ofsialic acid is from about 0.1 to 10 mg sialic acid/nostril/day. 12.Method of claim 8, wherein the pH of composition comprising sialic acid,preferably in aqueous solution, is from 2.0 to 4.0.
 13. Method of claim8, wherein the pH of composition comprising sialic acid, preferably inaqueous solution, is from 2.5 to 3.7.
 14. Method of claim 8, wherein thepH of composition comprising sialic acid, preferably in aqueoussolution, is from 2.8 to 3.2.
 15. Method of claim 8, wherein the dailydosage of sialic acid is delivered in from 2 to 8 administrations perday.
 16. Method of claim 8, wherein the composition further comprises athixotropic agent.
 17. Method of claim 1, wherein the sialic acid isadministered orally.
 18. Method of use of claim 17, wherein the dailydosage of sialic acid is from 20 to 200 grams.
 19. Method of use ofclaim 17, wherein the daily dosage of sialic acid is from 50 to 150grams.
 20. Method or use of any one of claim 17, wherein the dailydosage is administered in from 1 to 20 doses.
 21. Method or use of anyone of claim 17, wherein the sialic acid is administered as an aqueoussolution.
 22. Method of claim 21, wherein the aqueous solutioncomprising an additional agent selected from the group consisting of aflavoring agent, a stabilization agent and a preservative agent, whereinthe additional agent does not naturally occur with sialic acid.
 23. Themethod of claim 1, wherein the subject is at risk for infection bySARS-CoV-2.
 24. The method of claim 1, wherein the subject has COVID-19.25. Method of claim 2, wherein the sialic acid is elected from the groupconsisting of n-acetylneuraminic acid (NANA) and n-glycolylneuraminicacid (NGNA).
 26. Method of claim 25, wherein the sialic acid is NANA.27. Method of claim 2, wherein the sialic acid is administeredintranasally.
 28. Method of claim 27, wherein the effectiveconcentration of sialic acid is from about 0.1 to about 100 mg/ml in anaqueous solution.
 29. Method of claim 27, wherein the effectiveconcentration of sialic is from about 0.5 to about 50 mg/ml in anaqueous solution.
 30. Method of claim 28, wherein the daily dosage ofsialic acid is from about 0.1 to 100 mg sialic acid/nostril/day. 31.Method of claim 28, wherein the daily dosage of sialic acid is fromabout 0.1 to 10 mg sialic acid/nostril/day.
 32. Method of claim 28,wherein the pH of composition comprising sialic acid, preferably inaqueous solution, is from 2.0 to 4.0.
 33. Method of claim 28, whereinthe pH of composition comprising sialic acid, preferably in aqueoussolution, is from 2.5 to 3.7.
 34. Method of claim 28, wherein the pH ofcomposition comprising sialic acid, preferably in aqueous solution, isfrom 2.8 to 3.2.
 35. Method of claim 28, wherein the daily dosage ofsialic acid is delivered in from 2 to 8 administrations per day. 36.Method of claim 28, wherein the composition further comprises athixotropic agent.
 37. Method of claim 2, wherein the sialic acid isadministered orally.
 38. Method of use of claim 37, wherein the dailydosage of sialic acid is from 20 to 200 grams.
 39. Method of use ofclaim 37, wherein the daily dosage of sialic acid is from 50 to 150grams.
 40. Method or use of any one of claim 37, wherein the dailydosage is administered in from 1 to 20 doses.
 41. Method or use of anyone of claim 37, wherein the sialic acid is administered as an aqueoussolution.
 42. Method of claim 41, wherein the aqueous solutioncomprising an additional agent selected from the group consisting of aflavoring agent, a stabilization agent and a preservative agent, whereinthe additional agent does not naturally occur with sialic acid.
 43. Themethod of claim 2, wherein the subject is at risk for infection bySARS-CoV-2.
 44. The method of claim 2, wherein the subject has COVID-19.